This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The winter-type of Seasonal Affective Disorder (SAD) is widely accepted. However, recurrent mood disorders most commonly decompensate in spring and fall. Moreover, during spring there is a robust and highly replicated suicide peak worldwide (Petridou et al. 2002, Maes et al. 1993). The cause of this spring depression and suicide peak is unknown. Because (a) therapeutic and experimental administration of certain cytokines (e.g., blood chemicals, such as interferon-? [IFN-?]) results in depression (Pollmacher et al. 2002, Reichenberg et al. 2001), (b) allergic reactions in the nasal mucosa cause cytokine release from mast cells, eosinophils, and other mononuclear cells, and (c) tree-pollen concentration rises dramatically in spring, we hypothesize that in subjects with recurrent mood disorders the presence of specific anti-tree-pollen IgE antibodies will be associated with worsening depression in spring and a similar relationship with ragweed in fall. One possible mechanism of the depression-causing effect of inflammation is the activation of an enzyme (indoleamine 2,3 deoxygenase [IDO]) by certain cytokines secreted during allergic inflammation (e.g., IL-4, IFN-?), which "derails" tryptophan (TRP), a blood chemical from which serotonin is made, into production of kynurenine (KYN), a toxic compound. Previous studies show that a) acute TRP depletion is accompanied by mood worsening (Delgado et al 1990), b) cytokine levels directly correlate with mood worsening in experimental paradigms (Reichenberg et al. 2001), and c) the decrease of the TRP/KYN ratio induced by the therapeutic IFN administration positively correlates with depression (Capuron et al. 2003). Seasonal allergy is a common condition. Arbes et al. (2005) reported that 54% of National Health and Nutrition Examination Surveys (NHANES II and III) participants had a positive skin prick test for at least one allergen. Several studies show a link between depression and seasonal allergy (Timonen et al. 2002, 2003, Marshal et al. 2002). Given the temporal "vicinity" of suicide/depression peaks and tree-pollen peaks, we explored an epidemiologic association between suicide and tree-pollen exposure and reported an increase in suicide in women during and after peak-tree-pollen exposure (Postolache et al. 2005). Our long-term goal is to identify inflammation-mediated triggers for depression decompensation and suicide peak in spring using a concentric approach with clinical, epidemiological, postmortem brain tissue, and animal studies. Specific aim 1: To assess the relationship between positive IgE anti-pollen and spring and/or fall mood worsening in subjects with recurrent mood disorders. Hypothesis 1a: IgE anti-tree-pollen positive subjects will have a greater increase in depression scores during the peak- vs. pre-tree-pollen intervals compared with subjects with no allergen specific IgE antibodies (Phadiatop negative control subjects). Hypothesis 1b: The rate of decompensation during vs. before exposure to pollen will be greater in IgE anti-pollen positive subjects than the rate of decompensation in control subjects. Specific aim 2: To explore a quantitative relationship between certain markers of allergic inflammation (e.g., allergy related cytokines, TRP/KYN ratio) and the severity of depressive symptoms in IgE anti-pollen positive subjects. Hypothesis 2a: The change in depression scores from pre-peak to peak pollen intervals will positively correlate with changes in allergy symptom scores. Hypothesis 2b: The change in depression scores from pre-peak to peak pollen intervals will positively correlate with the changes in blood levels of IL-4, IL-13, and IFN-?. Hypothesis 2c: The change in depression scores from pre-peak to peak pollen intervals will negatively correlate with TRP/KYN ratios.